Table 3: Recovery and repeatability of bisphenols (10, 40, 80 ng/mL, n=8) in 70% VG / 30% PG using the SPE combined with LC–MS/MS. SD = standard deviation.


10 ng/mL Compound Bisphenol A Bisphenol AP Bisphenol E Bisphenol F Bisphenol S Bisphenol Z


Recovery (%)


96.3 40 ng/mL


SD %RSD Recovery (%)


4.8 5.0 93.8 80 ng/mL


SD %RSD Recovery (%)


1.7 1.8 97.0 93.4 17.4 18.6 105.4 14.9 14.1 107.8 106.0 93.2 102.0 3.9 2.3 7.7 3.7 2.5 7.6 92.3 92.3 94.7 1.5 1.6 2.2 2.4 4.9 5.1 96.5 96.8 91.0 102.3 17.8 17.4 110.7 11.3 10.2 107.9 SD %RSD 6.7 6.9 6.6 6.1 3.9 4.1 2.2 2.3 5.8 6.4 4.7 4.4


Conclusion


A sensitive SPE method combined with LC-MS/MS was developed and validated for six bisphenols in e-liquids (70% VG 30% PG), showing good linearity, recoveries of 91.0 to 110.7% and good repeatability ranging from 1.6 to 18.6 %RSD.


Application of the method to sixteen commercial e-liquids identifi ed bisphenol A in one sample and bisphenol E in three samples. The sample containing bisphenol A would exceed the EFSA tolerable daily intake under typical use. These results highlight consumer exposure to bisphenols and the need for further investigation of their presence in e-liquids. This method, using the Microlute®


CP HLB 96 well plate, provides a reliable tool for monitoring and supporting risk assessment of bisphenols in e-liquids. References


1. S. E. Jackson, H Tattan-Birch, L. Shahab, J. Brown, Trends in long term vaping among adults in England, 2013-23: population based study, BMJ, 2024, 386


Table 4: Bisphenol concentrations (mean ± SD, n=4) in commercial e-liquids analysed using the validated method of SPE combined with HPLC–MS/MS.


Analyte Concentration (ng/mL) Sample Flavouring


1 2 3


Unfl avoured Mint Mint


4 Passionfruit 5 6 7 8 9 10 11 12 13 14 15 16


Mixed berries


Mixed berries


Mixed berries


Melon


Mixed berries


Mixed berries


Apple Pear


Mixed berries


Mixed berries


Cream Energy drink


Mixed berries


Bisphenol A


<LOQ <LOD <LOD <LOD


<LOD <LOD <LOD <LOD


4.65 ± 0.29


<LOD <LOD <LOD <LOD <LOD <LOD <LOD


Bisphenol AP


<LOD <LOQ <LOD <LOD


<LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD


Bisphenol E


<LOQ <LOD <LOD <LOD


<LOD <LOD <LOQ <LOD <LOQ


0.30 ± 0.02


0.23 ± 0.01


<LOQ <LOD


0.26 ± 0.04


<LOD <LOD


Bisphenol F


<LOD <LOD <LOD <LOD


<LOD <LOD <LOQ <LOD <LOQ <LOD <LOD <LOD <LOD <LOD <LOD <LOD


Bisphenol S


<LOD <LOD <LOD <LOD


<LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD


Bisphenol Z


<LOD <LOD <LOD <LOD


<LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD


The validated SPE and LC-MS/MS method was applied to sixteen commercial e-liquids, each prepared in quadruplicate. Four samples (9, 10, 11 and 14) contained quantifi able levels of bisphenols. Bisphenol A was detected in sample 9, while bisphenol E was present in samples 10, 11 and 14.


Sample 9 contained 4.65 ng/mL of bisphenol A, which with a median daily e-liquid consumption of 4.6 mL [20], this corresponds to a daily intake of 21.39 ng. For an average adult (73.7kg [21]), this exceeds the EFSA tolerable daily intake of 0.2 ng/kg bodyweight/day by approximately 1.45 fold.


The remaining three e-liquids contained a lower level of bisphenol (<0.30 ng/mL), specifi cally bisphenol E. However, as toxicological data for bisphenol E is limited, its health effects remain unclear. These fi ndings highlight the need to identify the sources of bisphenols in e-liquids and help better evaluate potential risks to the consumers.


2. L. Mohammadi, D. D. Han, F. Xu, A. Huang, R. Derakhshandeh, P. Rao, A. Whitlatch, J. Cheng, R. J. Keith, N. M. Hamburg, P. Ganz, J. Hellman, S. F. Schick, and M. L. Springer, Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels, Arteriosclerosis, Thrombosis, and Vascular Biology, 2022, 42, 11


3. A. Moshensky, C. S. Brand, H. Alhaddad, J. Shin, J. A. Masso-SilvaIra, I. Advani, D. Gunge, A. Sharma, S. Mehta … L. E C. Alexander, Effects of mango and mint pod-based e-cigarette aerosol inhalation on infl ammatory states of the brain, lung, heart, and colon in mice, 2022, eLife, 11, 67621


4. X. Meng, X. Guo, Z. Peng, C. Wang, R. Liu, Acute effects of electronic cigarettes on vascular endothelial function: a systematic review and meta-analysis of randomized controlled trials, European Journal of Preventive Cardiology, 2023, 30(5), 425-435


5. M. J. Mears, H. L. Hookfi n, P. Bandaru, P. Vidal, K.I. Stanford, and L. E. Wold, Electronic Nicotine Delivery Systems and Cardiovascular/Cardiometabolic Health, Circulation Research, 2023, 132, 9


6. L. Honeycutt, K. Huerne, A. Miller, E. Wennberg, K. B. Filion, R. Grad, A. S. Gershon, C. Ells, G. Gore, A. Benedetti, B. Thombs, M. J. Eisenberg, A systematic review of the effects of e-cigarette use on lung function, NPJ Prim. Care Respir. Med., 2022, 32, 45


7. D. N. Bhatta, S. A. Glantz, Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis, Am. J. Prev. Med., 2020, 58(2), 182-190


8. L. P. Hariri, M.D., Ph.D., B. M. Flashner, M.D., D. J. Kanarek, M.D., W. J. O’Donnell, M.D., A. Soskis, M.D., D. R. Ziehr, M.D., A. Frank, M.D., D. C. Christiani, M.D., E-Cigarette Use, Small Airway Fibrosis, and Constrictive Bronchiolitis, 2022, NEJM Evid., 1, 6


9. M. W. Marbrey, S. M. Cripps, R. Huang, B. M. Kistner, A. Somany, E. S. Douglas, K. M. Caron, Flavored e-cigarettes modulate embryo development, fetal growth, and potentiate early fetal demise without nicotine, 2025, Communications Medicine, 5, 373


10. A. Vallée, M. Eid, A. Feki, J-M. Ayoubi, Maternal vaping and pregnancy adverse outcomes: A systematic review and meta-analysis, 2025, 38(5), 101951


11. M. L. Novak, G. Y. Wang, The effect of e-cigarettes on cognitive function: a scoping review, Psychopharmacology (Berl), 2024, 241(7), 1287-1297


12. M. Yuan, S. J. Cross, S. E. Loughlin, F. M. Leslie, Nicotine and the adolescent brain, J Physiol., 2015, 593(16), 3397-3412


13. P. Kubica, D. Osiecka, A. Kabir, N. P. Kalogiouri, V. F. Samanidou, Comparative study of bisphenols in e-cigarette liquids: Evaluating fabric phase sorptive extraction, ultrasound-assisted membrane extraction, and solid phase extraction techniques, Talanta, 2025, 283, 127096


14. P. Fenichel, N. Chevalier, F. Brucker-Davis, Bisphenol A: An endocrine and metabolic disruptor, Annales d’Endocrinologie, 2013, 74(3), 211-220


15. N. G. Khan, J. Correia, D. Adiga, P. S. Rai, H. S. Dsouza, S. Chakrabarty, S. P. Kabekkodu, A comprehensive review on the carcinogenic potential of bisphenol A: clues and evidence, Environ. Sci. Pollut. Res. Int., 2011, 28(16), 19643-19663


16. I. Cimmino, F. Fiory, G. Perruolo, C. Miele, F. Beguinot, P. Formisano, F. Oriente, Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease, 2020, 21(16), 5751


17. E. A. Salami, O. A. Rotimi, The impact of Bisphenol-A on human reproductive health, Toxicology Reports, 2024, 13, 101773


18. Commission Regulation (EU) 2024/3190 of 19 December 2024 on the use of bisphenol A (BPA) and other bisphenols and bisphenol derivatives with harmonised classifi cation for specifi c hazardous properties in certain materials and articles intended to come into contact with food, amending Regulation (EU) No 10/2011 and repealing Regulation (EU) 2018/213, https://eur-lex.europa.eu/eli/reg/2024/3190/oj/eng (Accessed September 2025)


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